A team of scientists from Germany has decided efficacy therapies currently used in treating a new variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including variants B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil) ). Their findings reveal that variants B.1.351 and B.1.1.248 can escape a humoral immune response induced by therapeutic antibodies, vaccinations, or natural SARS-CoV-2 infection. Studies are currently available at bioRxiv* preprint server.

Background

Since its emergence in December 2019, the highly contagious and deadly SARS-CoV-2, the pathogen that causes coronavirus disease 2019 (COVID-19), has infected more than 108 million people and claimed more than 2.3 million lives globally. In the global effort to control the spread of the virus, a lot of research has been done to find effective therapeutic strategies against COVID-19. Currently, several antiviral drugs and reused therapeutic antibodies are used to treat critical COVID-19 patients. As a protective measure, several potential vaccines targeting the viral spike protein have received emergency use approval from the relevant authorities.

In the next phase of the pandemic, several new variants of SARS-CoV-2 have emerged, including variants B.1.1.7 (UK), B.1.351 (South Africa), and B.1.1.248 (Brazil). Several mutations found in these variant spike proteins have been found to significantly increase their infectivity. Additionally, there are preliminary studies suggesting that this variant may be more virulent and is likely to increase the mortality rate related to COVID-19. Since most of the antibodies and therapeutic vaccines currently available primarily target the SARS-CoV-2 protein spike, potential concern is increasing about the effectiveness of current therapeutic interventions in preventing the spread and death of the emerging variant.

In the current study, scientists have evaluated the effectiveness of viral entry inhibitors, monoclonal antibodies, and vaccines in preventing infection by British, South African, and Brazilian SARS-CoV-2 variants.

Study design

Scientists use human and animal cell lines to do this in vitro trial. To analyze the effectiveness of virus entry inhibitors against the SARS-CoV-2 variant, they used angiotensin-converting enzyme 2 (ACE2), cellular protease inhibitors (TMPRSS2), and membrane fusion inhibitors (EK1 and EK1C4). To determine whether this variant is resistant to the humoral immune response, scientists thoroughly analyzed the efficacy of anti-SARS-CoV-2 antibodies obtained from three types of sources: 1) therapeutic monoclonal antibodies (Casirivimab, Imdevimab, and Bamlanivimab); 2) plasma samples collected from critically ill COVID-19 patients; and 3) serum samples collected from people vaccinated with the BioNTech / Pfizer vaccine (BNT162b2).

An important observation

Although there is evidence to suggest increased transmission of the emerging SARS-CoV-2 variant, current research scientists have not observed any significant differences in host cell entry dynamics between wildtype viruses and British, South African, and Brazilian variants. In particular, the wildtype spike protein and all tested variants of SARS-CoV-2 showed comparable efficiency in entering host cells.

Interestingly, the entry of wildtype variants and mutations into host cells was significantly blocked by dissolved ACE2, TMPRSS2 inhibitors, and inhibitors of membrane fusion. Compared with the wildtype virus, the variant shows a higher susceptibility to soluble ACE2-mediated inhibition. Likewise, the Brazilian variant showed a higher susceptibility to membrane fusion inhibitors. These observations suggest that virus entry inhibitors may potentially be used to prevent infection mediated by the mutated variant of SARS-CoV-2.

Although showing comparable cell-virus interaction dynamics, significant differences in antibody-mediated neutralization were observed between wildtype viruses and mutated variants. Among the monoclonal antibodies tested, Imdevimab demonstrated comparable efficacy in inhibiting entry of host cells by all viral variants. In contrast, the South African and Brazilian variants exhibited partial and complete resistance to Casirivimab and Bamlanivimab. However, all the antibodies tested showed high potency in inhibiting the British variant.

Neutralizing antibodies generated in response to SARS-CoV-2 infection is expected to provide protection against reinfection. To determine efficacy recovery plasma For the treatment of viral variants, COVID-19 plasma samples obtained by patients with high neutralizing properties of the wild-type spike protein were tested against all virus variants. The findings revealed that entry of host cells via spike proteins from the South African and Brazilian variants was less efficiently inhibited by the majority of the plasma samples tested. This suggests that people previously infected with the wildtype SARS-CoV-2 were only partially protected from the South African and Brazilian variants.

Regarding vaccine-mediated protection, the findings reveal that a large proportion of serum samples obtained from BNT162b2 vaccinated individuals had a lower efficiency in inhibiting surge-driven entry of host cells compared to that observed for wild and variant SARS-CoV-2 strains and variants. English.

Learn significance

The study revealed that current therapeutic interventions are less effective in inhibiting the SARS-CoV-2 variants of South Africa and Brazil, and thus, rigorous implementation of non-pharmaceutical control measures is needed to contain transmission.

* Important Notice

bioRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered a convincing guide, guide health-related clinical / behavioral practice, or be treated as defined information.